Cyclosporine for the treatment of psoriasis.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to C N Ellis.
Explore the source record for details and available documents.
The effect of Adriamycin on rat heart mitochondrial DNA was determined by initially labelling the DNA with [Me-14C]thymidine. Animals subsequently received intravenously either Adriamycin (10 mg/kg) or saline (1 ml/kg) (control group). Animals later received [Me-3H]thymidine and were killed at 6, 14, 24 and 36 h after this. The heart mitochondrial DNA was separated into the linear, non-supercoiled and supercoiled forms by ultracentrifugation on formamide/sucrose sedimentation gradients, and the amount of 14C and 3H incorporated into the various forms of the DNA was determined by scintillation counting. The data suggest that Adriamycin may cause breakage of the mitochondrial DNA helix, and that it slows the rate of mitochondrial DNA synthesis and the formation of complete DNA molecules. These experiments show that Adriamycin does interact with heart mitochondrial DNA, and may explain the cardiac dysfunction association with Adriamycin use.
A technique which will separate superhelical, intact nonsuperhelical, and damaged mitochondrial DNA molecules by use of sedimentation gradients of formamide-sucrose is described. This technique can be used to detect damage to the mitochondrial DNA helix.
Retinoids have and will continue to revolutionize dermatologic therapy in a manner analogous to the development of topical corticosteroids. Isotretinoin, for example, has made nodulocystic scarring acne an eminently treatable condition. The dermatologic armamentarium now includes a powerful new agent, etretinate, which will radically change the approach to psoriasis (and other keratinizing disorders). Although each new retinoid is developed with the aim of maximizing specific therapeutic effects and minimizing toxicity, the fact remains that the major side effects of retinoid treatment are those of hypervitaminosis A syndrome. Optimal clinical utilization of new retinoids is best accomplished by an assessment of what is currently known about retinol absorption, metabolism and organ-specific effects, as well as by a thorough understanding of hypervitaminosis A syndrome. In this paper, hypervitaminosis A syndrome is reviewed as a paradigm of retinoid side effects.
Two hundred sixty-eight patients with mild to moderate acne vulgaris completed a multicenter, double-blind, controlled study comparing isotretinoin 0.05% gel with its vehicle. Patients were treated twice daily for up to 14 weeks. Efficacy was measured by counting facial inflammatory and noninflammatory lesions and by grading acne severity initially and at 2- to 3-week intervals throughout the study. The isotretinoin 0.05% gel proved to be statistically more effective than vehicle in reducing inflammatory lesions after 5 weeks and in reducing noninflammatory lesions and acne severity grade after 8 weeks. Except for two patients who dropped out because of irritation, isotretinoin 0.05% gel was well tolerated.
Twenty-six patients with a history of hospitalization for severe psoriasis were evaluated with regard to their use of inpatient therapy before and during therapy with etretinate. The duration of the pretherapy period and the etretinate treatment period averaged 5 and 4 years, respectively. Use of etretinate nearly eliminated inpatient therapy among these patients. Twelve of the patients stopped etretinate; their use of hospitalization for psoriasis remained below pre-etretinate levels in the two years after etretinate therapy was stopped. Etretinate therapy represents an effective and economical alternative to hospitalization for psoriasis treatment.
Etretinate is a valuable addition to the treatment of psoriasis. Because of its numerous side effects, it should be reserved for only pustular, erythrodermic, and severe cases of plaque-type psoriasis. Many patients whose psoriasis has been recalcitrant to conventional therapy may greatly benefit from this drug.
Etretinate is a retinoid given orally for the treatment of psoriasis and many other dermatoses. Side effects are similar to the hypervitaminosis A condition. Etretinate represents a substantial advance in dermatologic therapy.
Since lipemia is commonly induced by retinoid therapy, we investigated the effects of etretinate administration on glucose metabolism by obtaining five-hour oral glucose tolerance tests in 23 patients before and after 20 weeks of etretinate therapy for psoriasis. Compared with pretreatment values, peak and aggregate levels for serum glucose and aggregate levels for serum insulin were significantly lower during therapy. The changes were not associated with obesity, weight loss during treatment, or pretherapy glucose tolerance or insulin secretion level. Of 11 patients with impaired or diabetic glucose tolerance prior to therapy, eight patients had improved glucose tolerance after 20 weeks of etretinate treatment. Despite inducing hypertriglyceridemia in most patients, etretinate therapy is associated with a reduction in glucose levels in response to a glucose load.
Recent studies indicate that antidepressant medications may be effective treatments for dermatologic disorders such as chronic urticaria and angioedema, nocturnal pruritus in atopic eczema, and postherpetic neuralgia, even in the absence of coexisting psychopathologic conditions. Their efficacy may be related to their antihistaminic, anticholinergic, and centrally mediated analgesic effects and appears to be independent of their antidepressant effect. It is likely, therefore, that more dermatologists will be prescribing these drugs without a psychiatric consultation.
In a double-blind trial, 21 patients with severe plaque psoriasis were randomly assigned to receive oral cyclosporine, 14 mg/kg/d, or its vehicle. After four weeks of therapy the 11 cyclosporine recipients had the following response to treatment: two had total clearing and six improved markedly, two moderately, and one minimally; whereas ten vehicle-treated patients showed no change or minimal improvement. Vehicle-treated patients, after a switch to cyclosporine for four weeks, demonstrated impressive improvement similar to that seen in patients who initially received only cyclosporine. Moderate or marked improvement or total clearing was noted in 17 (81%) of 21 and 20 (95%) of 21 after one and four weeks of therapy, respectively. Mitotic figures and leukotriene B4 levels in lesions decreased 86% and 64%, respectively, after seven days of cyclosporine therapy. Mononuclear (including activated T cells) and polymorphonuclear leukocyte infiltrates were markedly reduced in lesions of all patients after seven days of cyclosporine therapy. These results suggest that psoriasis may have an immunologic basis mediated by activated T cells and/or other immune cells; if a long-term regimen with a favorable efficacy-side effect ratio can be determined, cyclosporine would be a significant advance in the treatment of psoriasis.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
In a double-blind fashion, we compared the effect of topical application of 1% indomethacin cream or 1% meclofenamate cream with the effect of vehicle therapy alone in thirty patients with psoriasis. After 4 weeks' treatment of bilaterally symmetric psoriatic plaques, the indomethacin-treated sides were worse than the vehicle-treated sides in fourteen of twenty patients (p less than 0.01); the meclofenamate-treated sides were worse than the vehicle-treated sides in seven of ten patients (p less than 0.05). We suspect that the nonsteroidal anti-inflammatory drugs contributed to the maintenance of our patients' psoriasis by altering the arachidonic acid transformation cascade.
One hundred three patients entered a study to evaluate the effects of oral meclofenamate sodium therapy on psoriasis. The first 4 weeks of the study were double-blind, with patients receiving either meclofenamate or placebo. Most patients receiving meclofenamate had no change in their psoriasis, in comparison with their pretherapy condition. There was no difference in the response of the psoriasis between the group taking meclofenamate and the group taking placebo. Eighty-nine patients continued in a 4-week open trial of meclofenamate. Approximately one third of the patients showed improvement, but this result appeared to be related to the open trial design. Since oral meclofenamate therapy was not associated with frequent worsening of psoriasis, it is an appropriate treatment for psoriatic arthritis.
A 40-year-old man with severe psoriasis developed painless muscle stiffness coinciding with four successive courses of etretinate therapy. Peripheral nerve block extinguished the increased muscle tone. Our patient's symptoms resembled those of the stiff-man syndrome. Increased muscle tone is a potential side effect of etretinate treatment and must be distinguished from the common musculoskeletal symptoms observed in patients taking retinoid therapy.
Explore the source record for details and available documents.